A hallmark symptom of ME, Post-exertional malaise, is intolerance to previously trivial effort such as walking to the mailbox, running an errand or grocery shopping, taking a shower or brushing teeth, and deterioration of health from persistent or repeated exertion.[5][6][7][8][9][10][11] Myalgic encephalomyelitis is usually a relapsing-remitting disease with new symptoms occurring either in discrete relapses (or “crashes”) or accruing over time.[12] The National Organization for Rare Disorders (NORD) states: "Symptoms and their severity can fluctuate over the course of the illness, even from hour to hour."[13] The US National Institutes of Health notes that sensitivity to noise, light and chemicals may force patients to withdraw from society.[14]

ME does not have a cure, though treatments including the antiviral Ampligen (now approved for use on ME/CFS patients in Argentina) and immune system modulator Rituximab are being trialled.[15] There is a progressive form of ME but it is rarer than the relapsing-remitting type.[16]

There is a controversial view that ME is not a chronic infectious or autoimmune disease, but rather a psychosocial illness triggered by infection or stress and with a "high attack rate in females compared with males".[19] The BPS model is being applied to ME, CFS and PVFS by psychiatrists in the UK. However, Dr. VanElzakker said, “Everyone here [at Harvard] recognizes that it’s a neuroimmune condition and approaches it that way.”[20]

The UK Oxford criteria (the US Institute of Medicine report has called for its retirement)[31] and the US CDC Fukuda criteria (used in some research worldwide) are not describing ME but instead describe Chronic fatigue (CF). CF should not be confused with CFS. Many patients and ME organizations believe CFS must not be confused with ME nor its diagnostic criteria used to describe, diagnose or research ME.

The signs and symptoms of ME can be similar to other medical problems, "such as cancer, multiple sclerosis, lupus, brucellosis, or another condition."[32] Additional testing may be needed to help distinguish ME from these other problems.

"The first phase is an epidemic or endemic (sporadic) infectious disease generally with an incubation period of 4 to 7 days; in most, but not all cases, an infection or infectious process is evident."[33]

Secondary Chronic Phase

"The second and chronic phase follows closely on the first phase, usually within two to seven days; it is
characterized by a measurable diffuse change in the function of the Central Nervous System. This
second phase is the persisting disease that most characterizes M.E."[34]

Presentation

"The initial presentation takes one of two forms: a severe, incapacitating prolonged illness, or an apparent remission followed by increasing relapses until the patient is forced to recognize exertional limitation. The most common initial symptoms reported are: Pain in the spine, neck or head; mild fever and flu-like symptoms; nausea or vomiting; flaccid muscle weakness; and muscle pain or tenderness."[35] For some people, ME is triggered by Hepatitis B vaccination [36], blood transfusion[37], or chemical poisoning[38][39] (See: Countess of Mar), although it is now thought organophosphate poisoning is a different illness.[40][41]

Later course

"The later course of ME. is difficult to predict, and may either become consistently severe, improve to a plateau, or be markedly relapse-remitting. In some, even prolonged severe incapacitation can be relieved by unpredictable remission, although relapse is always possible. The degree of impairment and complexity depends on the degree of diffuse brain injury and end organ involvement."[42]

Subgroups/types

"The evidence for subgroups is strengthened by research using heterogeneous CFS criteria, although this artificial heterogeneity also hampers consensus. It is likely that subtypes exist within the ME milieu based on the clinical findings, history, and perhaps gender of patients."[43]

ME relapses are often a result of over-activity, but can occur without warning with no obvious inciting factors. Exposure to increased sensory information in light, sound, and movement can provoke a sensory storm.

Infections, such as the common cold, influenza and gastroenteritis, also increase the risk for a relapse. Heat and cold can transiently increase symptoms.

Pregnancy can directly affect the susceptibility for relapse. Later pregnancy appears to offer a natural protection against relapses, and there are anecdotal reports of postpartum remission. However, pregnancy does not seem to influence long-term disability.

Although much is known about abnormalities in ME., the reasons why they occur are not known. There are two ME. conferences held in the UK each year attended by international research luminaries, and other conferences held worldwide.

ME is a complex disease in which the immune and neurological systems appear dysregulated and in conflict, producing a wide variety of findings.

The problem is that most of the research in recent years has been conducted on people with CFS. This is a heterogeneous population, and includes patients with psychiatric disorders, as well as vitamin and nutritional deficiencies (especially vitamin D) and post-viral states such as ME.

According to a strictly immunological explanation of CFS, the inflammatory processes triggered by T cells create leaks in the blood-brain barrier (a capillary system that should prevent entrance of T-cells in the nervous system). These leaks, in turn, cause a number of other damaging effects such as swelling, activation of macrophages, and more activation of cytokines and other destructive proteins such as Rnase-L. A reduced ability to move metabolites in and out of cells (channelopathy) has been implicated in this process. This may also be applicable to ME.

Some evidence shows viral infection of muscle and brain in at least a proportion of sufferers. This triggers inflammatory processes, stimulating other immune cells and soluble factors like cytokines and antibodies. A model for late ME has been proposed analogously to post-polio syndrome in which repaired nerve tissue forms inappropriately [The Late Effects of ME: Can they be distinguished from the Post-polio syndrome?]. Radiological research on ME has shown hypoperfusion of the brain stem and an abnormal response to exertion, but research on CFS is often inconsistent and must be interpreted with caution. For example, a reduced volume of grey matter may be a result of a lack of activity and is reversible with cognitive behavior therapy.

An inquest into the death of Sophia Mirza from ME found inflammation of the dorsal spine ganglia and liver abnormalities. However, she had co-morbid disorders.

Hemodynamic abnormalities are widely found, including serum and RBC hypovolemia, NMH, and cerebral hypoperfusion. Vascular and endothelial abnormalities have been published by MERUK. However, none of these studies used research criteria for ME so the results may not be applicable to ME.

Some cardiologic features such as cardiac insufficiency, inverted T-waves and myofiber disarray have been reported in CFS and recently added to by findings of reduced Q-value. This has led clinician and researcher Dr. Paul Cheney to posit that CFS is form of partially compensated cardiomyopathy in which orthostatic intolerance and rapid fatiguability are secondary protective mechanisms. Due to the heterogeneity of the population, a single cause is unlikely, but one-third of people with ME have abnormalities when tested with Holter monitors.

Although risk factors for myalgic encephalomyelitis have been identified, no single definitive virus has been found in all cases, which has led to the claim that ME is a common end path of a variety of infectious insults.[45][46][47][48] It is still possible ME involves some combination of both environmental and genetic factors. Various theories try to combine the known data into plausible explanations.[49][50] Although most accept an infectious explanation, several theories suggest that ME is an inappropriate immune response to an underlying condition, a theory bolstered by the observation that there is sometimes a family history of autoimmune disease.[51] There is also a shift from the Th1 type of helper T cells, which fight infection, to the Th2 type, which are more active in allergy and more likely to attack the body.[52][53]

Other theories describe ME as an immune response to a chronic infection. The association between ME and the Coxsackie B, HHV-6, and HHV-7 viruses[54][55][56] suggests a potential viral contribution in at least some individuals. Others believe ME may sometimes result from a chronic infection with spirochetal bacteria, such as Lyme disease. Another bacterium that has been implicated in ME is Chlamydia pneumoniae.[57] Protein findings relating to several infections have seen found in the oligoclonal bands ME patients.[58]

The Vagus nerve infection hypothesis accounts for why so many different viral onsets could be responsible. The Vagus nerve runs from the brain stem and throughout the body and has an impact on many body systems.

There is no known cure for ME. Treatments for sleep problems, headaches and pain are utilized by some doctors for some patients although these are treating symptoms and not ME itself. Success of treating symptoms of ME is not well researched or documented.

As observed in many autoimmune disorders, ME is more common in females than males; the mean sex ratio is approxmately 2-3 females for every male.[60] In children the sex ratio is approximately equal.[61]